Mixing and/or reconstitution system

ABSTRACT

Systems and methods for mixing and/or reconstituting drugs are presented. A system may include an injection device, a vial, a needle, and a base station. The device has a chamber containing a first material. The vial has a chamber containing a second material. A drive unit of the base station moves the vial and/or the housing of the device relative to each other into an activated position. In the activated position, the needle is fluidly connected with the vial&#39;s chamber, and the drive unit is connected to a driver that moves the plunger in the axial direction of the device such that during fluid connection of the needle with the vial&#39;s chamber the first material is expelled from the device&#39;s chamber into the vial&#39;s chamber or the second material is expelled from the vial&#39;s chamber into the device&#39;s chamber.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is the national stage entry of InternationalPatent Application No. PCT/EP2018/081369, filed on Nov. 15, 2018, andclaims priority to Application No. EP 17306597.0, filed on Nov. 17,2017, the disclosures of which are incorporated herein by reference.

TECHNICAL FIELD

This disclosure refers to a mixing and/or reconstitution system, inparticular a drug mixing and/or reconstitution system, a base stationthereto, a supporting unit and a respective method.

BACKGROUND

Certain drugs are ideally administered in a liquid form, injectedsubcutaneously for the optimal therapeutic effect. However, some ofthese liquid drugs are unstable, having a shelf live that is relativelyshort. This can be a problem both for prophylactic treatments, wherepatients must inject themselves on a regular basis and therefore want tokeep a reasonable supply of drug at home, and for emergency treatments,where patients need to keep a supply of the drug to hand but may notneed it for weeks or longer.

In this case often drugs in a concentrated liquid form or lyophilized(freeze-dried) drugs are used, which usually comprise separatecomponents, namely a powder or liquid which is much more stable andtherefore has a long shelf life, and a diluent liquid. These componentsare typically supplied in separate vials and the user must reconstitutethe drug prior to injection. Such reconstitution is often a complexprocess with many steps. Also, there is the risk during thereconstitution process at various points that, if the user is notcareful, the drug can be contaminated. Therefore, there is a need for asystem and a method which removes the possibility of user error andprovides a well reconstituted drug in a short time.

From document US 2013/0296807 A1 a device for automatic reconstitutionand delivering a drug to a user and a method thereof is known. There isa need for a system or injection device which reduces the possibility ofuser error and provides an easy and automatic operation.

SUMMARY

The above problem is solved by the base station defined in claim 1. Itis further solved by the system defined in claim 3 and the methoddefined in claim 7.

In particular, a mixing and/or reconstitution system presented hereincomprises

-   -   a device containing a first material within a first chamber,        further comprising a housing and a plunger,    -   a vial containing a second material within a second chamber,        wherein at least one of the first material and the second        material is a fluid,    -   a base station comprising at least one drive unit, a first slide        and a driver, and    -   a needle,

wherein the device and the vial are attachable to the base station in aninitial position in which the device and the vial have a pre-defineddistance to each other, wherein the needle is attached to the device andfluidly connected with the first chamber of the device,

wherein in the initial position the at least one drive unit is connectedto the first slide that moves the vial and/or the housing of the devicerelative to each other in an axial direction of the device along apre-defined distance into an activated position, in which the needle isfluidly connected with the second chamber and

wherein in the activated position the at least one drive unit isconnected to the driver that moves the plunger in the axial direction ofthe device along a pre-defined distance such that during fluidconnection of the needle with the second chamber the first material isexpelled from the first chamber of the device into the second chamber ofthe vial or the second material is expelled from the second chamber ofthe vial into the first chamber of the device.

The present disclosure particularly refers to the mixing and/orreconstitution of a first drug component formed by or contained withinthe first material and a second drug component formed by or containedwithin the second material. Reconstitution is the rehydration of alyophilized (freeze dried) drug (e.g. first drug component) by a diluent(e.g. second drug component). The term mixing refers to any otherintermixing of any first and second drug component.

In one embodiment the first material is a fluid drug component and thesecond material is a solid drug component. In another embodiment, thematerial is a fluid which is expelled into the other chamber.

In a further embodiment the housing may be formed as a hollowcylindrical element. The plunger may be slidable accommodated within thehousing of the device at its proximal end. The plunger may close thefirst chamber, e.g. at its proximal end. The needle may be releasableattachable at the distal end of the device.

The vial may comprise a seal which may cover the vial, e.g., at itsfront end of the neck. The seal closes the second chamber hermetically.

The main advantage of the above described drug mixing and/orreconstitution system with a base station, a vial and a medical device,preferably an injection device, for example in the form of a syringe orautoinjector, wherein the device and the vial are attachable to the basestation in an initial position in which the device and the vial have apre-defined distance to each other, consists therein, that it automatesthe mixing and/or reconstitution operation, thereby removing all manualsteps, thereby reducing possible user error. The device may bedisposable or reusable.

In one embodiment the drive unit has two motors, wherein the first andthe second motors drive different elements of the device and/or thevial.

According to one aspect of the present disclosure, the needle is fluidlyconnectable to the device by means of a threaded connection or otherknown connection, for example to the housing of the injection device.

In a further embodiment the housing of the device contains the firstfluid chamber which may be pre-filled. The device first material may becontained in a cartridge.

Further, the first slide may move the vial and/or the housing axially inboth axial directions of the device.

The base station may comprise a recess at the upper side of its housingwhich is adapted to receive and releasably fix the device and the vialor an assembly comprising the device (described below), and the vialwhen locked within the supporting unit. Therefore the recess at leastpartly corresponds to the outer circumference of device and the vial orthe outer circumference of the assembly. The base station may be adaptedsuch (e.g. its recess) that the axial direction of the device and thevial is tilted with regard to the horizontal direction when fixed at thebase station, such that e.g. the vial is positioned higher than thedevice. The base station may comprise a locking feature which may lock(and unlock) the vial and the device or the assembly that is explainedbelow at a pre-defined position.

In another embodiment a sleeve-like, e.g. hollow cylindrical, supportingunit is provided which is adapted to form the assembly mentioned abovecomprising the device, the vial, the needle, wherein the supporting unitis adapted such that it fixes the device and the vial at a pre-definedrelative position, wherein the needle is attached to the device andfluidly connected with the first chamber of the device, wherein theassembly is attachable to the base station in the initial position ofthe device and the vial. Further, a needle boot may be provided, whereinthe needle boot is attached to the device such that it covers theneedle. The needle boot may be collapsible and, if applicable, alsoremovable.

The supporting unit may comprise two parts which may form a releasableconnection, e.g. a hinge connection. Alternatively or additionally, thesupporting unit may form a unit with the vial. The assembly may beself-supporting.

In one embodiment the supporting unit may form a first recess and asecond recess on the inner side such that the supporting unit locks thepre-filled device and the vial in a locked position during transit andstorage, preventing them from making contact with each other. Therefore,the device may be fixed such in the first recess and the vial is fixedsuch in the second recess that they have a predetermined distance fromeach other.

In another embodiment, in the case that the mixing and/or reconstitutionis conducted within the second chamber of the vial afterwards at least apre-defined fraction of the mixed and/or reconstituted drug isdischarged from the second chamber of the vial into the first chamber ofthe device. In particular, a full volume of the reconstituted drug maybe discharged from the vial into the first chamber of the injectiondevice. In one embodiment the driver may discharge the mixed and/orreconstituted drug.

According to another aspect of the present disclosure, in case thedevice is an autoinjector, the device may comprise a needle guard and amechanism coupled to the needle guard which unlocks the plunger. In oneembodiment the mechanism is a locking pin or other catch mechanism.Additionally, the autoinjector may comprise a fluid chamber, wherein thefluid is for example air, which hermetically seals the proximal end ofthe autoinjector with the plunger and wherein the base station comprisesa fluid pump, wherein the fluid pump is fluidly connected to the fluidchamber in the activated position. In order to pull the plunger thefluid pump may work in reverse. In one embodiment a needle of the basestation may pierce a septum of the fluid chamber for fluid connectionwith the fluid pump.

The driver may be connected to a second slide or an overpressure fluidprovided by a fluid pump in order to move the plunger for mixing and/orreconstitution, wherein the second slide is connected with the plungerand the overpressure fluid acts on the plunger, respectively.

The above problem is further solved by a base station comprising atleast one drive unit, a first slide and a driver,

wherein the base station is adapted such a device, a vial and a needleare attachable to the base station in an initial position in which thedevice, the vial and the needle have a pre-defined distance to eachother,

wherein the device contains a first material within a first chamber andcomprises a housing and a plunger,

wherein the vial contains a second material within a second chamber,wherein at least one of the first material and the second material is afluid,

wherein in the initial position the at least one drive unit is connectedto the first slide that moves the vial and/or a housing of the devicerelative to each other in an axial direction of the device along apre-defined distance into an activated position, in which the needle isfluidly connected with the second chamber and

wherein in the activated position the at least one drive unit isconnected to the driver that moves the plunger in the axial direction ofthe device along a pre-defined distance such that during fluidconnection of the needle with the second chamber the first material isexpelled from the first chamber of the device into the second chamber ofthe vial or the second material is expelled from the second chamber ofthe vial into the first chamber of the device.

As indicated above the base station may further comprise a vibratingunit, preferably vibrating at a frequency between 60 Hz and 50 kHz, morepreferred between 60 Hz and 200 Hz or between 10 kHz and 50 kHz, adaptedto transmit a mechanical vibration to the vial of the assembly or theinjection device, when the assembly is in the activated position.

In a further embodiment the base station may further comprise a heaterelement adapted to heat the first and/or second chamber, for example toa temperature within a temperature range between 18° C. and 30° C.,preferably between 18° C. and 26° C. when the assembly is in theactivated position reducing the likelihood that a cold mixture causesdiscomfort during drug injection into the patient. A thermistor(temperature measurement sensor) may be provided at the base station toensure that the drug is not overheated. Alternatively, heat may besupplied through a solid-state heat pump, i.e. a Peltier device.

The above problem is further solved with a sleeve-like supporting unit,

wherein the supporting unit is adapted to fix a device and a vial at apre-defined relative position within the supporting unit forming anassembly, wherein the device comprises a first chamber wherein a needleis attached to the device and fluidly connected with the first chamberof the device.

Additionally, a needle boot may be provided, wherein within the assemblythe needle boot is attached to the device such that it covers theneedle.

The above problem is further solved by a mixing and/or reconstitutionmethod using a device and a vial,

wherein the device contains a first material within a first chamber, andfurther comprises a housing and a plunger,

wherein the vial contains a second material within a second chamber,wherein at least one of the first material and the second material is afluid,

the method comprising the following steps:

-   -   attaching a needle to the device and fluidly connecting the        needle with the first chamber of the device,    -   attaching the device with the needle and the vial to a base        station in an initial position prior mixing and/or        reconstitution in which the device and the vial have a        pre-defined distance to each other,    -   in the initial position moving the vial and/or the housing of        the device relative to each other in an axial direction of the        device along a pre-defined distance into an activated position,        in which the needle is fluidly connected with the second chamber        and    -   in the activated position moving the plunger in the axial        direction of the device along a pre-defined distance such that        during fluid connection of the needle with the second chamber        the first material is expelled from the first chamber of the        device into the second chamber of the vial or the second        material is expelled from the second chamber of the vial into        the first chamber of the device.

According to a further aspect of the present disclosure the method maycomprise the further step that after mixing and/or reconstitution of thedrug in the activated position the vial and/or the housing of the deviceis moved in one axial direction of the device along a pre-defineddistance such that the needle is fluidly disconnected from the secondchamber.

Additionally or alternatively, the method my comprise the further stepthat prior the initial position an assembly comprising the device, thevial, the needle and a sleeve-like supporting unit is formed, whereinthe needle is attached to the device and fluidly connected with thefirst chamber of the device and wherein the supporting unit fixes thedevice and the vial at a pre-defined relative position.

In one embodiment the further step that during forming the assembly aneedle boot is used and is attached to the device such that it coversthe needle.

The needle boot may be collapsed when the vial and/or the housing aremoved relative to each other in an axial direction prior the needle isfluidly connected with the second chamber.

In one embodiment the method may comprise the additional step that aftera pre-determined time of mixing and/or reconstitution of the drug theplunger may be used into another axial direction of the injection devicealong a pre-defined distance by the drive unit such that at least apre-defined fraction of the reconstituted drug is discharged from thevial into the first chamber of the injection device if the mixing and/orreconstitution of the drug is conducted in the second chamber of thevial.

In a further embodiment of the method the device is an autoinjectorcomprising a needle guard, a mechanism coupled to the needle guard whichunlocks the plunger, and a fluid chamber hermetically sealing theproximal end of the autoinjector with the plunger, wherein a fluid pumpof the base station is fluidly connected with the air chamber duringfixing the assembly at the base station in an activated position. In oneembodiment the air pump moves the plunger in any axial direction of theautoinjector.

In a further embodiment the base station comprises a vibrating unit,preferably vibrating at the frequencies indicated above, wherein themethod comprises the additional step of transmitting a mechanicalvibration to the vial of the assembly or the injection device after thefirst material is expelled from the first chamber and into the secondchamber of the vial or after the second material is expelled from thesecond chamber of the vial into the first chamber of the injectiondevice.

In another embodiment the method the base station comprises a heaterelement as indicated above which preferably heats the second chamberafter the first material, is expelled from the first chamber and intothe second chamber of the vial.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows a concept sketch of a first embodiment of an injectiondevice in a sectional view.

FIG. 2 shows the first embodiment of an injection device in a sectionalview prior activation.

FIG. 3 shows the device of FIG. 2 after activation.

FIG. 4 shows the device of FIG. 2 during reconstitution.

FIG. 5 shows the device of FIG. 2 at the beginning of injection.

FIG. 6 shows the device of FIG. 2 after injection.

FIG. 7 shows a detail of the device of FIG. 2 in a sectional view.

FIG. 8 shows a detail of the plunger of the device of FIG. 2 .

FIG. 9 shows a concept sketch of another embodiment of an injectiondevice with a primary package in a sectional view.

FIG. 10 shows another embodiment of an injection device with a primarypackage in a sectional view.

FIG. 11 shows the embodiment of FIG. 10 during a first step of amixing/reconstitution process in a sectional view.

FIG. 12 shows the embodiment of FIG. 10 during a second step of amixing/reconstitution process in a sectional view.

FIG. 13 shows the embodiment of FIG. 10 during a third step of amixing/reconstitution process in a sectional view.

FIG. 14 shows the embodiment of FIG. 10 during a forth step of amixing/reconstitution process in a sectional view.

FIG. 15 shows the syringe of the embodiment of FIG. 10 prior injectionin a sectional view.

FIG. 16 shows an injection device and a detail of a mixing unit of anembodiment of an inventive system in a sectional view as a conceptsketch.

FIG. 17 shows an injection device received by a mixing unit of anotherembodiment of an inventive system in a perspective and sectional viewprior activation of the mixing and/or reconstitution step.

FIG. 18 shows the system of FIG. 17 prior to insertion of the injectiondevice into the mixing unit in a sectional view.

FIG. 19 shows the system of FIG. 17 after insertion of the injectiondevice into the mixing unit in a sectional view.

FIG. 20 shows the system of FIG. 17 after activation of the mixingand/or reconstitution step and the initial electromagnetic fieldproduced by the electromagnetic unit in a sectional view.

FIG. 21 shows the system of FIG. 17 during the mixing and/orreconstitution in a sectional view.

FIG. 22 shows the system of FIG. 17 after the mixing and/orreconstitution step and during withdrawal of the injection device fromthe mixing unit in a sectional view.

FIG. 23 shows the injection device of the system of FIG. 17 during drugadministration.

FIG. 24 shows a slug-like element of the system of FIG. 17 in aperspective view.

FIG. 25 shows a distal section of a plunger of another embodiment of aninjection device in a perspective and sectional view.

FIG. 26 shows a first set of force profiles for different active coilsets of the electromagnetic unit of the mixing unit of FIG. 17 in adiagram in which the electromagnetic force on the slug-like element isshown as a function of the axial position within the opening.

FIG. 27 shows a second set of force profiles for different active coilsets of the electromagnetic unit of the mixing unit of FIG. 17 in adiagram in which the electromagnetic force on the slug-like element isshown as a function of the axial position within the opening.

FIG. 28 shows a third set of force profiles for different active coilsets of the electromagnetic unit of the mixing unit of FIG. 17 in adiagram in which the electromagnetic force on the slug-like element isshown as a function of the axial position within the opening.

FIG. 29 shows an injection device and a detail of a base station ofanother embodiment of an inventive system in a longitudinal section as aconcept sketch.

FIG. 30 shows another embodiment of an inventive system comprising anassembly with an injection device, a vial and a supporting unit as wellas a base station in a perspective view from the side, wherein the basestation is shown partially transparent.

FIG. 31 shows the disposable subassembly from FIG. 30 in an explodedview from the side.

FIG. 32 shows the assembly of FIG. 31 prior fixing at the base stationin a longitudinal section.

FIG. 33 shows another embodiment of an inventive system comprising anassembly with an injection device, a vial and a supporting unit as wellas a base station in a perspective view from the side, wherein the basestation is shown partially transparent.

FIG. 34 shows the disposable subassembly from FIG. 33 in an explodedview from the side.

FIG. 35 shows the subassembly of FIG. 34 in a longitudinal section priorreconstitution.

FIG. 36 shows the subassembly of FIG. 34 in a longitudinal section afterreconstitution.

FIG. 37 shows the base station of FIG. 33 in a perspective view from theside, partially transparent.

DETAILED DESCRIPTION

The first embodiment of an injection device in form of a syringe 100depicted in FIGS. 2 to 8 comprises a housing 101 and a needle 102attached at its distal end. The principle of operation is demonstratedby FIG. 1 . The needle 102 is in fluid communication with a firstchamber 105 accommodated within the housing 101, wherein the firstchamber 105 contains a first drug component, for example a lyophilizeddrug.

A plunger 107 is movable within the housing 101 in an axial(longitudinal) direction with regard to the syringe 100 or housing 101,wherein the plunger 107 closes the first chamber 105 at its proximalend.

Within the plunger 107 a second chamber 109 is provided containing asecond drug component, for example a diluent. The second chamber 109 isclosed at its distal end by a lower piston 111 and at its proximal endby an upper piston 112. The lower piston 111 and the upper piston 112are movable within the plunger 107. The plunger 107 is formed as asleeve-like element, wherein the hermetic seal of the first chamber atthe proximal end of the first chamber 105 is provided by a distal endsection 108 which has a bigger diameter than the remaining section ofthe plunger (except a handle 113). The diameter of the distal endsection 108 corresponds to the inner diameter of the first chamber 105.The proximal end of the plunger 107 is formed as the handle 113. Thedistal end section of the plunger 107 comprises a, for examplecylindrical through hole 114. As well as admitting the passage of fluid,this through hole 114 acts as a guide for a stud-like cotter pin 117,ensuring that piston 111 moves in a stable axial fashion.

The needle 102 is covered at its distal end by a needle boot 115. Theneedle boot 115 is required to prevent pressure differences fromallowing air into the syringe 100.

In the initial position the lower piston 111 forming a seal between thefirst chamber 105 and the second chamber 109 while it is sitting in thearea of an even inner surface of plunger 107. To activate mixing and/orreconstitution process of the syringe 100 shown in an initial state inFIG. 2 , in a proximal stroke, a user pulls back on the plunger 107 outof the syringe 100 into a proximal direction using the handle 113 (seein FIG. 3 the fully pulled back position of plunger 107). This causes aregion of low pressure to form inside the syringe 100, in particular thefirst chamber 105. The pressure further decreases as the plunger 107 isfurther pulled back. The plunger 107 is prevented from moving back toits original position shown in FIG. 2 by a ratchet system betweenplunger 107 and housing 101 (see FIG. 8 ). An outer projection fromplunger 107 runs inside a track in housing 101. This projection issprung to engage with a ratchet 101 a in the track, so that plunger 107can only move in one direction, until it has completed the full extentof its travel: then, the protrusion is guided into a smooth return track101 b. The ratchet system with ratchet 101 a ensures that the plunger107 is pulled far enough out of the syringe 100 before it begins to moveback into the syringe 100 along return track 101 b, thereby guaranteeingthat a minimum level of suction is generated (see FIG. 3 ). The suctionprovided by the low pressure is needed to pull the first drug componentthrough the through hole 114 within the plunger 107 and also to promotemixing of the first drug component and the second drug component withinthe first chamber 105.

The pressure difference between the inside of syringe, in particularinside the first chamber 105 and the second chamber 109, and atmospherecreates a force on the lower piston 111. This force is transferredthrough the second drug component contained in the second chamber 109and onto the upper piston 112. They are thereby caused to move theplunger 107 down. The cotter pin 117 thereby moves through the throughhole 114 and the lower piston 111 until the upper piston 112 hits thelower piston 111 (see FIG. 3 ). The cotter pin 117 and/or the lowerpiston 111 comprise a compressible outer surface which interacts with aset of longitudinal ribs 120 (web-like elements) provided at the distalend of the inner surface of the plunger 107 forming an uneven innersurface (see FIG. 7 ). When the lower piston 111 is pushed into theuneven area (ribs) the seal is broken. These ribs 120 force gaps to openup around the lower piston 111 and fluid can go through and thereforeopen a fluid communication path between the second drug componentcontained in the second chamber 109 and the first drug componentcontained in the first chamber 105 via the through hole 114. The seconddrug component flows out the distal end of the plunger 107 and into thefirst chamber 105 of the syringe 100 (see FIG. 4 , it shows the positionin which the second drug component has completely emptied into the firstchamber 105). All of the second drug component will have passed into thefirst chamber 105 of the syringe 100 before the plunger 107 is pulledback completely. As plunger 107 moves back further, pressure in chamber105 drops to near vacuum.

Once the plunger 107 has completed its stroke in the proximal direction,the ratchet mechanism will permit it to move back into the syringe 100until pressure has equilibrated within the syringe 100 and atmosphere.This return is sudden, and the abrupt equilibration promotes mixingbetween the first and the second drug component in chamber 105.

At this point visual check of mix clarity is needed before the mixedand/or reconstituted drug comprising the first drug component and thesecond drug component can be injected. If it has not been fully mixed,the user must manually shake the device to fully mix the drug. Once thedrug is fully mixed, it can be injected using the plunger 107 by movingit into distal direction by means of handle 113 as with any standardsyringe (see FIG. 6 showing the syringe 100 post injection).

When plunger 107 is moved to inject drug, the pressure increase withinthe syringe 100 causes the upper and lower pistons 111, 112 to move intoproximal direction until a snap or clip member 112 a at the proximal endof the upper piston 112 and snap or clip member 107 a at the innersurface of the plunger 107 interact and mechanically lock (see FIG. 5 ,realized for example by a hook and a protrusion). This prevents anyincrease of pressure inside the syringe 100 from forcing the lowerpiston 111 and the upper piston 112 further back into the plunger 107and therefore the second drug or the mixture of first and second drugcannot move back into the plunger 107. In this position the lower piston111 does not interact with the ribs 120 of the plunger anymore and hencethe lower piston 11 closes the second chamber 109. Note that dependingon various detail design features, this may have already occurred duringthe sudden equilibration of pressure described above.

In an alternative embodiment, at the point where the user visuallychecks the clarity of the mix comprising the first and the second drugcomponent, instead of manually shaking the syringe 100 it is allowedthat the plunger 107 is continuously pulled back in order to create aregion of low pressure in 105 again. This cyclical process is allowed bythe ratchet mechanism forming a closed loop, which the mechanism of 107can go around repeatably. The user may pull back the plunger and releaseit as many times as they like until the first and second drug componentsare fully mixed.

In a further embodiment the injection device is an autoinjector. Thisautoinjector may be constructed such that it includes an automatedmovement of the plunger in the reverse direction so that mixing of thefirst and second drug component is performed without user intervention.An optical check of clarity of the mix comprising the first and seconddrug component is still required from the user so that the autoinjectorwould need to be able to continue the mixing cycle for as long as theuser deems necessary. This may be realized using the repeated creationof low pressure regions as outlined above.

The above mentioned communication between the first and the secondchamber 105, 109 is provided by breaking of the seal provided by thelower piston 111 within housing 107, as the lower piston 111 interactswith the ribs 120 of the plunger 107. Alternatively, a bypass pathwaymay be created which allows the second drug component to flow around thepiston 111. As a further alternative there may also be used some form ofneedle/septum interaction as depicted in FIG. 1 , where a needle 122attached to the distal end of the lower piston 111 pierces a membrane125 of the distal end section 108 of the plunger 107.

The needle 102 may be changeable and removably attachable to theinjection device.

In a further embodiment rather than the ratchet mechanism being insidethe injection device 100, it could be housed outside of the injectiondevice within a separate housing. The housing would hold syringe 100 andplunger 107, and guide their relative motion in the same way that theratchet achieved. This will save space in the disposable device, as itremoves a complex interaction between parts 100 and 107.

In a further embodiment a combined axial and rotational (twisting)motion could be conducted by the user to pull back the plunger 107,similar to those systems found in standard pen injectors, instead of theaxial movement described above.

In a further embodiment it is possible to include a needle shield in theinjection device. This shield would cover the needle 102 and retract asthe user pushes the device against their skin for injection. Once theneedle 102 is removed from the skin, the shield would move back intoplace and thereby activate a locking mechanism so that the user isunable to retract the needle shield again.

The above mentioned embodiments explained with reference to FIGS. 1 to 8have the advantage that they provide an improved user operabilitybecause the user needs only to pull back the plunger until it naturallysnaps back into the injection device. Further, the ratchet mechanismregulates the process so that the result is independent of user skill.Further, the user may perform a visual check of clarity of the mix ofthe first and second drug components. The user only needs to gentlyshake the injection device to ensure complete mixing of any residualfirst or second drug component. Additionally, during the reconstitutionprocess air is not introduced. The injection is analogue to the standardprocedure which the patient knows. Further, there is no danger ofcontamination during the mixing and/or reconstitution process as it alloccurs within a factory-sealed environment. The mixing of the first andsecond drug components is very predictable and consistent. Additionally,the user has only one disposable part and does not have to ensuresterility for any part as this is maintained throughout use. Althoughthere is use of a low pressure region to promote mixing of the first andsecond drug components, this low pressure does not have to be heldduring device storage.

The embodiment shown in FIGS. 10 to 15 and as a concept sketch in FIG. 9comprises a syringe 500 with a housing 501 and a needle 502 attached tothe distal end of the syringe 500. The needle 502 is in fluidcommunication with a first chamber 505 accommodated within the housing501 of the syringe 500. The first chamber 505 is defined at its proximalend by a plunger 507. The first chamber 505 comprises a first drugcomponent, for example a lyophilized drug. The needle 502 is suitablefor injection of a drug into a patient. A minimal volume of air is heldwith the first drug component within the first chamber 505.

Additionally, a primary package 510 is provided comprising a housing 510a (custom housing). The primary package 510 contains within a secondchamber 509 formed by its housing 510 a a second drug component, forexample a diluent, accommodated between a lower piston 511 and an upperpiston 512. The lower piston 511 and the upper piston 512 are bothmoveable within the housing 510 a of the primary package in an axialdirection, wherein the lower piston 511 is accommodated more proximalthan the upper piston 512. The lower piston 511 contains a septum sealwithin its body. Additionally, it comprises at its upper or distalsurface a recess or indentation 511 a. The upper piston 512 is incontact on its distal side with a compression spring 530 as a drivingmechanism which is initially compressed and held in place by a clipmechanism 536. A cap 535 on the distal end of the primary package 510sits over the clip mechanism 536, i.e. the cap covers the clip mechanism536 with the spring 530. When the cap 525 is pushed downwards, e.g. intoproximal direction, it will release the clip mechanism 536 and allow thespring 530 to apply an axial force into proximal direction to the upperpiston 512. At the proximal end of the primary package 510 attachmentmeans, for example one part of a luer-lock 537, is provided. As shown inFIG. 10 prior to activation of the mixing and/or reconstruction processthe primary package 510 is attached to the distal end of the syringe 500by the attachment means, for example the luer-lock 537. This luer-lock537 provides a seal to ensure that the exposed parts of the needle 502remain sterile until injection, e.g. the space around the needle 502 issealed during device assembly and remains so until immediately prior toinjection. Further, an O-ring 538 is provided which contacts the housing510 a of the primary package 510 and the luer-lock 537 forming anadditional seal.

A different attachment means between the syringe 500 and the primarypackage 510 can be used, rather than luer-lock. Any attachment mechanismmust remain secure over a shelf-life of one year and additionally beeasy to engage and disengage by hand.

In an initial position shown in FIG. 10 after attachment of the primarypackage 510 to the distal end of the syringe 500 by the luer-lock 537the needle pierces the lower piston 511 to a certain extend but does notpenetrate the septum seal within the body of the lower piston 511.

In order to start with the mixing and/or reconstitution process the userpresses on the cap 535 and moves it into proximal direction (see arrow540 in FIG. 11 ). Thereby, the clip mechanism 536 retaining thecompression spring 530 is disengaged and allows the compression spring530 to extend (see FIGS. 11 and 12 ). The disengagement may work in oneembodiment as follows. The upper piston 512 may comprise one flexibleclip or more than one flexible clips (not shown) which pass through ahole in the housing 510 a, and act against an upper face of housing 510a. The cap 535 comprises a recess (not shown) at its front end over therespective flexible clip. As cap 535 is pressed down, the clip entersthe respective recess. Each recess is chamfered so that as the clipsenter, they are compressed together, disengaging them from housing 510 aallowing the spring 530 to extend in axial direction. Both, the forcefrom the extending spring 530 and from the users hand can contribute topush the subsystem comprising the second drug component (the second drugcomponent plus the upper and the lower piston 511, 512) along an axialproximal direction of the primary package 510. Thereby the needle 502 isforced to penetrate the septum seal of the lower piston 511 therebyforming a fluid communication between the second chamber 509 and thefirst chamber 505 of the syringe 500. The lower piston 511 is stoppedfrom moving further by an end-stop feature within the primary package510, for example a projection 513 at the inner surface of the housing510 a (see FIG. 10 ). In this position the distal end of the needle 502is located within the recess 511 a of the lower piston 511. The upperpiston 512 is further forced to move into proximal direction and intothe direction of the lower piston 511 thereby increasing the pressurewithin the second chamber 509 and pushing the second drug componentthrough the needle 502 into the first chamber 505 (see arrow 541 in FIG.12 ).

The recess 511 a at the lower piston 511 allows the needle 502 toprotrude through the lower piston without ever touching the upper piston512 (see FIGS. 11 and 13 ). It is noted that the lower piston 511 andthe upper piston 512 eventually met when whole content of the seconddrug component is transferred from the second chamber 509 into the firstchamber 505. The recess 511 a has the advantage that if the upper piston512 contacts the lower piston 511 the needle 502 would not contact theupper piston 512 and consequently the flow of the second drug componentthrough the needle 502 would not stop. In another embodiment the recessmay be located in upper piston 512 rather than in lower piston 511, forthe same effect.

When the second drug component enters the first chamber 505 it will beunder substantial pressure which creates a high speed jet (for examplewith a fluid velocity of 2.5 m/s and faster, preferably with a velocityof 5 m/s and faster) in the case that the second drug component isfluid. This jet dislodges the first drug component and causes turbulentmixing. All of the second drug component will be mixed into the firstdrug component by the time the upper piston 512 finishes expelling ofthe second drug component into the first chamber 505. The spring 530generates all of this pressure to drive the second drug component andensures reliable and repeatable mixing independent of user strength orskill. The user may visually check that the first and second drugcomponents are fully mixed.

Then the user may unscrew (see arrow 542 in FIG. 14 ) or otherwisedetach the primary package 510 from the syringe 500. The syringe is nowready to inject (see FIG. 15 ) the mixed and/or reconstituted drugcontained within the first chamber 505.

In another embodiment rather than using a standard syringe 500 for theaccommodation of the first drug component, a cartridge could be used tobe placed in another device for injection.

In one embodiment the plunger 507 within the syringe 500 may be customshaped to improve the mixing resulting from the fluid jet. For example,the plunger 507 may comprise one or more concave cavities at its frontend defining the first chamber 505. Within such cavity the jet of fluidis deflected out to better penetrate the corners of first chamber 505.Alternatively or additionally, one or more vanes at the front end ofplunger 507 defining the first chamber 505 may achieve a similar effect.

In another embodiment the proximal end of the needle 502 within thesyringe 500 may be shaped so that a jet of fluid is directed towards theproximal direction, keeping the majority of turbulent mixing close tothe first drug component. For example, the proximal end of needle 502may have a bend so that the jet enters first chamber 505 at an obliqueangle, setting up swirl flows to promote mixing. Alternatively oradditionally, through holes within the side wall of the proximal end ofthe needle 502 may be provided in order to create multiple jets.

In a further embodiment the primary package 510 may be housed inside anautoinjector so that manual injection is not necessary. The autoinjectorwould have to allow removal or separation of the primary package 510prior to insertion.

In another embodiment the attachment of the syringe 500 and the primarypackage 510 may be more permanent. For example the syringe 500 and theprimary package 510 may be welded together, with the weld creating ahermetic seal that replaces the function of the seal 538 and theluer-lock connector 537. In this case, a mechanism must allow thesyringe 500 and the primary package 510 to separate before injection.This may be realized by a snap mechanism, wherein the housing 501 of thesyringe 500 and the housing 510 a of the primary package 510 may simplysnap apart under user pressure.

In a further embodiment, the primary package 510 may comprise twoseparate parts, one holds the spring and the other one holds just thesecond chamber with the second drug component and the upper and lowerpiston 511, 512. This would remove the need to weld the primary package510 together during manufacture. The parts would have to interlock priorattachment to the syringe 500.

In further alternative embodiments, the force for driving the upperpiston 512 may be generated not by a compressed spring 530 as explainedabove but instead by another driving mechanism, for example by a gasspring or by a linear electromechanical actuator.

In another embodiment the sizes of the first chamber 505 and the secondchamber 509 as well as the needle gauge can be customized in order tocreate a suitable jet profile for effective mixing of the particularfirst and second drug components.

The needle 502 could, instead of being staked into the syringe 500, bechangeable. In this case one needle may be used for mixing and/orreconstitution but the user swaps it for a separate, sterile needle forinjection.

In a further embodiment the mixing and/or reconstitution process may beactivated by movement of the primary package, for example its housing,rather than a pushing onto the cap 535. For example, when the userattaches the primary package 510 to the syringe 500 the lower and upperpistons 511 are automatically driven such that the needle 502 fullypenetrates the septum, starting the flow of the second drug componentinto the first chamber 505.

The advantage of the embodiment explained above with regard to FIGS. 9to 15 consists therein that the user convenience is extremely goodbecause the user has only to press a button on the distal end of thedevice and wait until mixing and/or reconstitution is complete. This maybe visually checked by the user. Then, the user may unscrew the syringe500 from the primary package 510, expels air by priming as usual andinjects the drug. There is no danger of contamination during the mixingand/or reconstitution process as it all occurs within a factory-sealedenvironment. The mixing is very predictable and consistent and the userhas only two disposable parts, namely the primary package 510 and thesyringe 500. The user does not have to ensure sterility for any part asthis is maintained throughout use.

The embodiment described in FIGS. 17 to 28 comprises an injection devicein form of a syringe 200 and a mixing unit in form of a base station250. The syringe 200 comprises a housing 201 with a first chamber 205and a plunger 207 which closes the first chamber 205 at its proximalend. At its distal end the plunger 207 forms a second chamber 209 withina respective inner space of the plunger 207. The first chamber 205contains a first drug component, for example a diluent, wherein thesecond chamber 209 contains a second drug component, for example alyophilized drug. Additionally, a moveable slug-like element 210 with amagnetic or paramagnetic characteristic is provided within the secondchamber 209. The distal end of the second chamber 209 of the plunger 207is covered by a seal 211. The seal may be realized by a foil ormembrane, for example comprising or consisting of an aluminum-polymerlaminate or a low-permeability polymer such as a cyclic olefin. At thedistal end of the housing 201 of the syringe 200 a needle 202 with aneedle cover 215 is attached. The needle 202 is in fluid communicationwith the first chamber 205 of the syringe 200. The needle cover 215protects the needle 202, avoids its contamination and prevents the userfrom needle sticks.

The slug-like element 210 may comprise or is composed of, for example,at least one of the following materials comprising sinteredNeodymium-Iron-Boron (NdFeB), preferably with a medical-grade coating,Samarium-Cobalt (SmCo) and Aluminum-Nickel-Cobalt (AlNiCo). The middleor main section of the element 210 is preferably formed as a cylinder.Alternatively, it may have a shape of a barrel or of a section of asphere. One distal end 210 a of this element 210, which is shown in FIG.24 in detail, may be shaped as a sharp tip to puncture the seal 211.Additionally, the proximal end 210 b of the element 210 may be taperedin order to help the element 210 to slide back up into the plunger 207,so that it does not get trapped between the plunger 207 and the innerwall of the syringe housing 201, thereby preventing full injection ofthe mixed and/or reconstituted drug.

The seal 211 may be provided such that it bursts in a way that does notcreate loose parts. Equally, the proximal end of the needle 202 may bemade too small for foil parts to enter, or a filter may be added insidethe syringe (e.g. at the distal end of the first chamber, within thefirst chamber 205) preventing that foil parts enter the needle 202.

The base station 250 comprises a series of electromagnetic coils 260 aplus milled steel pole pieces 260 b accommodated in between two adjacentelectromagnetic coils 260 a to guide the magnetic flux and improveefficiency. The electromagnetic coils 260 a and steel pole pieces 260 btogether form the electromagnetic unit 260. The electromagnetic unit 260encases a cylindrical opening 265 which is provided to receive thedistal end of the syringe 200. An inserted syringe 200 within theopening 265 is shown for example in FIGS. 17, 19, 20, and 21 . The basestation 250 further comprises a control unit 270 and a power supply withbatteries 273 in order to provide electrical energy for the componentsof the base station 250. Further, a button 275 is provided by pressingof which the mixing and/or reconstitution of the first and second drugcomponent may be activated by the user when the syringe 200 is insertedin the opening 265. The opening of the base station 250 may contain asensor for the syringe 200 recognizing the correct and full insertion ofthe syringe 200 within the opening 265. In case the sensor does notnotice a syringe 200 correctly inserted within the opening 265 anactivation of the button 275 shall not start the mixing and/orreconstitution step.

In the first step, the syringe 200 is inserted into the opening 265 ofthe base station 250 (see FIG. 18 ) so far that its body 201 is fullyreceived by the opening 265 (see arrow 213). By pushing the button 275the user activates the electromagnetic unit 260 energizing the coils 260a so that a large force into an axial direction of the syringe 200, forexample a distal direction, is exerted on the slug-like element 210during a pre-determined time period, causing it to puncture the seal211. Thereby it is allowed to the first and second drug component to mixwithin the first chamber 205, for example to reconstitute bothcomponents.

In one embodiment the base station 250 comprises a separate interlocksystem holding the syringe 200 within the opening 265 of the basestation 250 until mixing is complete.

Once the element 210 has punctured the seal 211 it is free to move alongthe entire length of the first chamber 205 into an axial direction ofthe syringe 200 back and forth (see arrow 214). FIG. 20 shows lines ofmagnetic flux with flux density, for the initial stage, in which theslug-like element 210 is accelerated in order to pierce the seal 211.The lines of the magnetic field are marked with the reference number262. Afterwards, the coils 260 a and the magnetic element 210 form abrushless linear motor, i.e. a Lorentz force device, whereby energizingdifferent coils in different directions and at different times causesthe element 210 to move backwards and forwards in the axial(longitudinal) direction (arrow 214) of the syringe 200 within apre-determined time period to effect mixing within the first chamber 205(see FIG. 21 ). In one embodiment the base station 250 comprises fourcoils 260 a accommodated side by side along the axial direction (seearrow 214), wherein at any one time, two coils 260 a are active (seeFIG. 20 ) alternating with the other two coils 260 a. The two activecoils 260 a are energized in opposite directions, and interact with thetwo magnetic poles of the element 210 to generate an axial force suchthat, in one step, one coil 260 a repels one magnetic pole of theelement 210 and the other coil 260 of the two active coils attracts theother magnetic pole of the element 210. Only energizing coils 260 aclose to element 210 improves the efficiency of the system. By settingprecise levels of power in each coil 260 a, the speed and position ofthe element may be accurately controlled. If each coil 260 a has aresistance of 40 Ohms, the drive system may include a boost powersupply, e.g. providing 200 V, driving the coils 260 a via a half bridgefor 0.1 seconds. This could generate 1 kW in the coils, which wouldgenerate the large forces needed to initially puncture the foil seal.The control unit 270 of the base station 200 provides a predefinednumber of cycles of energizing different coils of the electromagneticunit 260 that guarantees a homogenous reconstituted or mixed drug. Atthe end of the process (see FIG. 22 ), the element 210 rests in aposition within the previous second chamber 209 of the plunger 207whereby it does not hinder injection. As shown in FIG. 24 , the element210 has a tapered proximal end 210 b to help it re-enter the plunger207. By means of the control unit 270 which is connected with theelectromagnetic unit 260 a smooth slide of the element 210 into theplunger 207 is provided during injection.

Finally, as shown in FIG. 22 , the syringe 200 is removed from the basestation 250. In order to inject the mixed and/or reconstituted drugcontaining the first and the second drug component the user removes theneedle cover 215, expels any air from the syringe by means of primingand finally injects the drug mixture (see FIG. 23 ).

The FIGS. 26 and 27 show the forces generated at 10 W and 900 W for fivedifferent coils of the electromagnetic unit 260, respectively, for thegeometry shown in FIG. 17 . At 10 W, forces are ample to dislodge thesecond drug component and mix the first and second drug componentreliably. At 900 W, forces are adequate that the element 210 isaccelerated and punctures the seal 211, subject to the geometry of theslug-like element 210. This high power is only needed for a very briefperiod of time, namely the time in which the seal 211 is punctured, sototal energy used is low and the coils of the electromagnetic unit 260do not overheat.

In another embodiment an additional plate-like metal element 220, madefrom a soft magnetic material for example comprising steel, could beused to hold the paramagnetic or magnetic element 210 in place until thesyringe 200 is placed in the base station 250 and activated, and also tokeep the element 210 inside the plunger during injection. The plate-likeelement 220 is accommodated within the plunger 207 close to the proximalend of the second chamber 209 (see FIG. 25 ). The plate-like element 220is as close as possible to element 210, by making the wall between itand chamber 209 as thin as practical, preferably the thickness may beless than 1 mm. This means that element 220 can be small and stillprovide sufficient attraction to element 210. For example, element 220may have a thickness of more than 0.5 mm, preferably more than 1 mm. Theplate-like element 220 prevents that no amount of inadvertent agitationduring (e.g.) shipping or dropping the device prior to use will causethe seal 211 to rupture. In an alternative embodiment the element 220could be a separate element which the user has to remove or an elementthat is dislodged on insertion of the syringe 200 in the base station250. For example, the element may be a steel collar piece accommodatedaround the outside of housing 201 of the syringe 200, which is slid awayon insertion into base station 250. Anyhow, the element 220 generates asmall enough force that the coils of the electromagnetic unit 260 caneasily overcome it.

If the slug-like element 210 is a permanent magnet, it is preferred touse a medical-grade coating to prevent contact between the magneticmaterial and the first or second drug component.

Instead of using a moving magnetic material for the electromagneticelement 210 (a “Lorentz force” device or linear brushless motor), theelement 210 could made of a soft magnetic material, e.g. mild steel. Inthis case only one coil is needed to be activated at any time and thesyringe works as a simple electromagnetic, e.g. a solenoid actuator.FIG. 28 shows that such an actuator generates even higher instantaneousforces for a given power input but these forces vary more with theposition of the soft magnetic element within the first chamber 205 sothat the coils must be carefully sized/placed to avoid positions of theelement 210 in which no force is generated. If the element 210 is a softmagnetic material, it could be, for example, medical-grade stainlesssteel, in which case no coating is required. In that case, the magneticelement 210 may form sharp edges to more effectively puncture the foil.

In another embodiment instead of using a simple syringe, the injectiondevice can be complete autoinjector. The above explained process may beconducted as indicated above: the autoinjector containing the first andsecond chambers comprising the first and second drug component isinserted into the base station, the components are mixed and theautoinjector is removed ready to use.

As a further embodiment, e.g. for high-value drugs, it may beeconomically viable to include the electromagnetic unit, the powersupply and the control unit into a disposable component of the injectiondevice so that no separate base station is needed.

In a further embodiment the internal shape of the needle 202, of thefirst chamber 205 and of the housing 201 of the syringe 200 may bedesigned such that the element 210 will not hinder injection should theelement 210 remain in the first chamber 205 after mixing.

Rather than a syringe or an autoinjector, the injection device may be acartridge suitable for use with a separate injection device. In otherwords, it is a syringe, but missing the long plunger that enables a userto carry out injection, and also missing the needle: the injectiondevice includes the system for penetrating the skin, and also the systemfor driving injection.

The inventive system shown in FIGS. 16 to 28 comprising a syringe 200and a base station 250 for drug reconstitution and/or mixing isextremely good operationally because there is no danger of contaminationduring the reconstitution process as it all occurs within afactory-sealed environment. The disposable part comprising the syringe200 is very compact. The mixing/reconstitution is very predictable andconsistent with a low amount of steps. There is only one disposable partper injection. The design of this base station offers maximumflexibility across injection device types namely pre-filled syringes,autoinjectors and cartridges. The injection device does not need aneedle fitted in advance of reconstitution.

The embodiment of a drug reconstitution system shown in FIGS. 29 to 32comprises a prefilled injection device in form of a syringe 300 with ahousing 301 and a vial 308. The syringe 300 comprises a first chamber305 which contains a first fluid drug component, for example a diluent.The vial 308 comprises a second chamber 309 containing a second solidand/or fluid drug component, for example a lyophilized drug.Additionally, the system comprises a supporting unit 310 which consistsof, for example, two parts 310 a and 310 b (see FIG. 31 ) which may bereleasable connected to each other, e.g., by means of a snap connection.The syringe 300 is further connected to a needle 302, wherein the needle302 is covered by a needle boot 315. The syringe 300 further comprises aplunger 307 at its proximal end opposite from the distal end of thesyringe 300 which is connected to the needle 302. The plunger 307 ismovable within the housing 301 of the syringe 300 along an axial(longitudinal) direction of the syringe 300. The plunger 307 closes theproximal end of the first chamber 305. If the plunger 307 is moved inproximal direction an underpressure is generated within the firstchamber 305. If the plunger 307 is moved in distal direction the firstdrug component is expelled from the first chamber 305 through the needle302.

The drug reconstitution system further comprises a base station 350comprising a housing 351 and, within the housing 351, at least one driveunit 370.

The supporting unit 310 is formed like a capsule or a hollow cylinderwhich comprises two sections with different diameter when both parts 310a, 310 b shown in FIG. 31 are connected to each other (see FIG. 30 ).Alternatively, the connection of both parts 310 a, 310 b of thesupporting unit 310 may be a hinge connection. The supporting unit 310forms a first recess 311 and the second recess 312 on the inner side ofeach part 310 a, 310 b such that the supporting unit 310 locks thepre-filled syringe 300 and the vial 308 in a locked position duringtransit and storage, preventing them from making contact with eachother. Therefore, the syringe 300 is fixed such in the first recess 311and the vial 308 is fixed such in the second recess 312 that they have apredetermined distance from each other (see FIG. 32 ). For example, thefirst recess 311 and the second recess 312 each may comprise at leastone web or similar projection at its inner surface which forms a snapconnection with the housing 301 of the syringe and/or the needle boot315 or which forms a snap connection with the vial 308, for example atits neck section (see FIG. 32 ). If the syringe 300 and the vial 308 arefixed within the supporting unit 310 and both parts 310 a and 310 b ofthe supporting unit 310 are connected to each other, a self-supportingassembly is formed which locks the pre-filled syringe 300 and the vial308 in position, for example, during transit and storage, preventingthem from making contact with each other.

The vial 308 comprises a seal 313 which covers the vial 308 at its frontend of the neck. The seal 313 closes the second chamber 309hermetically.

The drive unit 370 of the base station 350 comprises for example a firstmotor and a second motor. Additionally, an optional high frequencytransducer 371 as a vibrating unit and further an optional heaterelement 372 are provided within the housing 351 of the base station 350.The base station 350 further comprises a recess 365 at the upper side ofthe housing 351 which is adapted to receive and releasably fix theassembly comprising the syringe 300, and the vial 308 when locked withinthe supporting unit 310. Therefore the recess 365 at least partlycorresponds to the outer circumference of the assembly.

In order to reconstitute a drug and to prepare the syringe 300 forinjection the assembly shown in FIG. 32 comprising the syringe 310, thesupporting unit 310 and the vial 308 is inserted into the recess 365 ofthe base station 350 by the user and fixed there. The syringe 300 withthe needle 302 and the vial 308 is now in the initial position. The basestation 350 has the following interfaces to the assembly shown in FIG.32 :

-   -   the vial, 308, is held stationary;    -   the syringe 300 engages, for example with its housing 301, with        a first linear slide 374 that is actuated in an axial direction        by a motor drive unit 370;    -   and plunger 307 engages with a second linear slide 375 that is        actuated in an axial direction by a second, independent, motor        drive unit (not shown).

The fixing of the assembly of FIG. 32 may be achieved either through:

-   -   passive clips, which the user can overcome to pull the assembly        out; or,    -   a separate motor drive unit can operate a clamping mechanism to        hold the assembly in place during the reconstitution process;        or,    -   the assembly shown in FIG. 32 can only engage/disengage with the        first and second linear slides when they are in their initial        positions.

In operation, in the position in which the assembly of FIG. 32 isinserted, that assembly may have to pass through slots in housing 351that align with the first and second linear slides. Once the drive unitshave begun to move, features on the assembly no longer align with theslots in housing 351, and the user cannot remove the assemblyprematurely. Thereby, the assembly is held at an angle in the basestation 350 with the vial 308 positioned higher than the syringe 300 sothat second component from the second chamber 309 of the vial 308 ratherthan air is drawn into the syringe 300 during preparation. This isrealized by the tilting angle of the recess 365 of the base station 300with regard to the opposite platform face 366 on which the base station350 stands. The base station 350 contains a feature to unlock the partsof the supporting unit 310 allowing the syringe housing 301 and the vial308 to move relative to each other when positioned within the recess 365of the base station 350. For example, this unlock feature may consist ofa flexible hook element inside supporting unit 310 which locks into afeature on the syringe housing 301, so that the two parts cannot moverelative to each other. A pin feature in recess 365 may penetrate asmall hole in supporting unit 310, to push the flexible hook element outof the way, enabling housing 301 to move relative to supporting unit310. Alternatively, rather than being a fixed pin, this unlock featurecould be actively driven, e.g. with a solenoid. The feature shouldremain unlocked as the assembly is removed from the base station 350, sothat the user can withdraw the syringe 300 for injection.

In the next step the first motor of the drive unit 370 drives thehousing 301 of the syringe 300 towards the vial 308 by means of thefirst slide 374. The needle boot 315 is compressed against the vial 308and the needle 302 is inserted into the seal 313 of the vial 308 forminga fluid connection with the second chamber 309 of the vial 308. Thesyringe 300 with the needle 302 is moved toward the vial 308 andinserted into the second chamber 309 for a pre-defined distance. At thesame time the second motor of the drive unit 370 moves the syringeplunger 307 by means of the second slide 375 towards the vial 308 at thesame rate so that the volume inside the first chamber 305 staysunchanged during this step. The vial 308 and the syringe 300 with theneedle 302 are now in an activated position.

In the next step, after the activated position of vial 308 and syringe300 is reached, with the first motor held stationary, the second motordrives the syringe plunger 307 towards the vial 308 by means of thesecond slide 375, expelling the first drug component, for example thediluent, into the second chamber 309 of the vial 308 forming a mixtureof the first drug component and the second drug component within thesecond chamber 309.

A range of mechanisms can be used to convert the rotational motion ofthe drive units 370 into a linear action on housing 301 of syringe 300and plunger 307. The unit shown in FIG. 30 comprises a lead screw, wherethe motor of drive unit 370 turns a threaded bar. There is a nut runningon the threaded bar, which is fixed both rotationally and axially to thefirst linear slide 374 that engages with housing 301 of syringe 300. Asthe threaded bar is rotated, the nut is driven along the threaded bar,driving housing 301 in an axial direction. The same may be provided bythe second linear slide 375 coupled to plunger 307. Alternatively, thethreaded bar can be fixed rotationally and axially to the profiledcomponent engaging with 301 or 307, and the nut is driven rotationallyby the motor. This nut can form part of the motor itself.

Once all first fluid drug component has been transferred into the secondchamber 309, the transducer 371 may agitate the vial 308 containing themixture of the first drug component and the second drug component,promoting mixing of, for example, the drug powder and the diluent. Thistransducer 371 may be a piezoelectric transducer, i.e. a piece ofpiezoelectric ceramic between two electrodes. If an oscillating voltageis applied to the electrodes, the thickness of the transduceroscillates, creating a pressure wave. Due to the inherently smalldisplacements of piezoelectric transducers, very good acoustic couplingis necessary between the transducer 371 and the vial 308. This is likelyto require at least a spring-loaded contact between the transducer andthe vial, or even a liquid- or gel-based coupling. Alternatively, thetransducer 371 may be an electromagnetic linear actuator, such as avoice coil or a solenoid. This operates at lower frequency, but thelarger displacements achievable mean that it is simpler to transmit theagitation into the mixture. Alternatively, a motor driving an imbalancedload (a vibration motor) could be used to generate the oscillatingpressure waves. At the same time or afterwards, the heater element 372may heat up the mixture to a pre-set temperature, for example in therange of 18° C. to 26° C., reducing the likelihood that a cold mixturecauses discomfort during drug injection into the patient. The heaterelement 372 may be a simple resistive element, generating heat when anelectric current passes through. A thermistor (temperature measurementsensor) would be necessary to ensure that it is not overheated, unlessthe system is designed so that it is physically impossible for any faultto lead to overheating. Alternatively, heat can be supplied through asolid-state heat pump, i.e. a Peltier device.

Once the second drug component is fully dissolved in the first drugcomponent or the other way around forming a reconstitution or once bothcomponents are mixed and—if applicable—the reconstitution or mixturereaches the correct temperature, the second motor drives the syringeplunger 307 by means of the second slide 375 into axial direction awayfrom the vial 308 drawing the mixture or reconstitution into the syringe300, namely from the second chamber 309 of the vial 308 into the firstchamber 305 of the syringe 300. Since the vial 308 is positioned higherthan the syringe 300, and the needle 302 is at the lowest point of thevial 308, the base station ensures that only the mixture orreconstitution of the second chamber 309 has drawn into the syringe 300,minimizing the air volume in the syringe 300. In the next step the firstmotor and the second motor of the drive unit 370 act together to pullthe syringe 300 and with it the needle 302 out from the vial 308. Theuser then takes the syringe 300 out from the recess 365 of the basestation 350, removes the supporting unit 310 from the syringe andmanually injects the reconstituted or mixed drug contained in the firstchamber 305 of the syringe 300. The vial 308 is a disposable device,wherein the syringe 300 may be a disposable or reusable device.

The embodiment of a drug mixing or reconstitution system shown in FIGS.33 to 37 is similar to the embodiment shown in FIGS. 29 to 32 but withan autoinjector 400 instead of the syringe 300. An element of thisembodiment of the system having the same last two digits of thereference number but a leading digit 4 instead of 3 corresponds to therespective element of the system shown in FIGS. 29 to 32 .

The autoinjector 400 may be a traditional spring driven design or onethat is actuated by a fluid, for example, air pressure. In thefollowing, the system is explained by means of an autoinjector 400actuated by air pressure which is provided to users with atmosphericpressure in an air chamber 414 initially. The system works similarlywith an autoinjector using a spring as the drug delivery energy source.

The drug reconstitution system comprises the autoinjector 400, a vial408 and a supporting unit 410 which comprises two parts 410 a and 410 bfor connecting to each other and fixing the autoinjector 400 and thevial 408 within forming an assembly for transit and storage in apre-defined distance or relative position to each other. Additionally, abase station 450 is provided.

The autoinjector 400 further comprises a first chamber 405 and a needle402. The first chamber 405 contains a first drug component, for examplea diluent. The vial 408 comprises a second chamber 409 containing asecond drug component, for example a lyophilized drug, and a seal 413covering the vial and closing its second chamber 409 hermetically. Thesystem comprises further a needle boot 415.

For reconstitution or mixing of the first and second drug components ofthe autoinjector 400 and the vial 408 the needle boot 415 is attached toa first recess 411 of the supporting unit 410 as shown in FIG. 36 .Then, the assembly is composed by connecting the first and second part410 a, 410 b of the supporting unit 410 to each other and inserting thevial 408 and the autoinjector 400 into their respective first and secondrecess 411, 412. For attachment of the autoinjector 400 to thesupporting unit 410 a needle guard 417 of the autoinjector 400 has to beretracted in order to expose the needle 402 which is then covered by theneedle boot 415 (see FIG. 35 ). The autoinjector 400 and the vial 408are fixed to the supporting unit 410 for example by a snap connection.

In order to reconstitute a drug with the system shown in FIGS. 33 to 37the assembly (see FIG. 35 ) is inserted into a recess 465 of the basestation 450 as shown in FIG. 33 . Now the autoinjector 400 and the vial408 are in an initial position. A feature on the base station 450unlocks the parts 410 a, 410 b of the supporting unit 410, allowing theautoinjector 400 with the needle boot 415 and the vial 408 to movetowards each other along an axial direction of the autoinjector 400 bymeans of a first slide connected to the drive unit 470. For example, theunlock feature may consist of a flexible hook element projecting fromthe inner surface of the supporting unit 410 which locks into arespective recess on outer surface of the autoinjector housing 401, sothat the supporting unit 410 and the autoinjector housing 401 cannotmove relative to each other. A pin feature in recess 465 may penetrate asmall through hole in supporting unit 410 when correctly attached to thebase station 450 within the recess 465, to push the flexible hookelement out of the way, enabling autoinjector housing 401 to moverelative to the supporting unit 410. Alternatively, rather than being afixed pin, this unlock feature could be actively driven, e.g. with asolenoid, or a second drive motor. Alternatively, instead of activatinga release mechanism inside supporting unit 410, the unlock feature couldfully open supporting unit 410 up, i.e. separate the two parts 410 a,410 b of the autoinjector housing. The unlock feature should remainunlocked as the assembly is removed from the base station 450, so thatthe user can withdraw the syringe 400 for injection.

In the next step, a needle of the base station 450 pierces a septum 418at the autoinjector body 401, allowing an air pump 473 of the basestation 450 to pump air in and out an autoinjector air chamber 414comprising the plunger 407. The needle is fluidly connected to the airpump 473. Then, a first motor of a drive unit 470 of the base station450 pushes the autoinjector 400 towards the vial 408. Thereby the needleguard 417 retracts further into the autoinjector body 401 and the needleboot 415 is compressed so that the needle 402 is inserted into the vial408, e.g. its second chamber 409, through the seal 413 for exampleformed as a rubber cap. The first slide connected with the drive unit470 engages with a feature on housing 401, and drives it axially. Arange of mechanisms can be used to convert the rotational motion of thedrive unit motor into a linear action on the autoinjector body 401. Themechanism shown in FIG. 37 is a lead screw, where the motor turns athreaded bar. There is a nut running on the threaded bar, which is fixedboth rotationally and axially to a first linear slide (e.g. a profiledcomponent) that engages with the autoinjector body 401. As the threadedbar is rotated, the slide is driven along the threaded bar, drivingautoinjector body 401 in an axial direction towards the vial 408 therebyinserting the needle 402 into the second chamber 409. The autoinjector400 and the vial 408 are now in an activated position.

Afterwards, a second motor of the drive unit 470 of the base station 450activates a mechanism of the autoinjector 400 to unlock a plunger 407 ofthe autoinjector 400 allowing the plunger 407 to move using a plungerlocking mechanism 420. The locking mechanism 420 exists so that once theautoinjector 400 is filled and primed, it does not release its storedenergy and inject drug until it is activated by the user. It is shown inFIG. 35 as a simple locking pin, but it can be any catch feature thatlocks the plunger in position. This catch is later released to initiatedrug delivery, e.g. the user presses a button to move the catch awayfrom the plunger, or the catch is released when the needle guard ispressed against the skin. However, it must also be operated by the basestation 450, in order that the base station 450 can perform mixing andpriming of the autoinjector 400. Therefore, second motor of the driveunit 470 releases the autoinjector plunger 407, for example by releasingthe catch of the locking mechanism 420. Then, driven by the drive unit470, the air pump 473 of the base station 450 pumps air into the airchamber 414 surrounding the plunger 407 via the needle which pierces theseptum 418 thereby pushing the plunger 407 towards the vial 408 to expelthe first drug component from the first chamber 405 at the same time.Accordingly, the first drug component of the first chamber 405 can nowbe mixed and/or reconstituted within the second chamber 409 of the vial408 with the second drug component.

For mixing and/or reconstituting, the base station 450 may vibrate thevial 408 at a high frequency using a transducer 471 (vibrating unit)and/or warm up the mixture within the vial 408 at the same time using aheater element 472. Once the mixture or reconstitution is prepared, theair pump 473 of the base station 450 works in reverse to pump air out ofthe air chamber 414 generating a vacuum in order to pull the plunger 407away from the vial 408 such that the drug mixture or reconstitution isdrawn into the first chamber 405 of the autoinjector 400. In the nextstep the second motor of the drive unit 470 activates the plungerlocking mechanism 420 to lock the plunger 407 in position again. Now,the air pump 473 pumps compressed air into the air chamber 414, thistime as the drug delivery power source. Then the first motor draws theautoinjector 400 out of the vial 408, allowing the user to remove theassembly 410 from the base station 450.

In order to use the autoinjector 400, the user pulls to remove the vial408 and the supporting unit 410 by opening the two parts 410 a, 410 b.This also removes the needle boot 415 from the autoinjector 400 in thesame step. Removal of the needle boot 415 has the additional advantagethat it removes the chance of injecting rubber debris from the needleboot 415 into the patient. This step also reveals the needle guard 417(see FIG. 36 ). Then, the user presses the needle guard 417 onto theinjection site, pushing the needle guard 417 into the autoinjector body401 and inserting the needle 402 into the patient. A feature of theneedle guard 417 activates the mechanism of the autoinjector 400 tounlock the plunger 407. In one embodiment of the unlock mechanism thereis an axial extension of needle guard 417 towards the locking mechanism420. As the needle guard 417 is pushed back into housing 401, thisextension engages with a ramp or similar mating feature in lockingmechanism 420, moving it out of the plunger 407 or otherwise disengagingthe locking mechanism. The plunger 407 then moves towards the needle 402under air pressure thereby providing injection of the mixture orreconstitution into the patient. Once the injection is finished, theuser removes the autoinjector 400 from the injection site and the needleguard 417 extends outwards under a spring force of a spring 419 to coverthe needle 402 again. The needle guard 417 also locks itself against theautoinjector body 401 to prevent needle 402 stick injuries.

In an alternative embodiment of the above explained autoinjector conceptactuated by air pressure an autoinjector concept using a spring as thedrug delivery energy source can be used. An inventive method isbasically the same except for during the mixing and/or reconstitutionstage the second motor of the drive unit 470 actuates the plunger 407 toexpel the first drug component into the second chamber 409 of the vial408. After mixing or reconstitution, the second motor withdraws theplunger 407, producing an underpressure within the first chamber 405 anddrawing the mixed or reconstituted drug into the autoinjector 400,namely its first chamber 405. Completion of this movement happens whenthe plunger 407 reaches its locking position at the proximal end,wherein this action may compress a delivery spring ready for drugdelivery at the same time. Activation happens analogously to the aboveembodiment, when the user presses the needle guard 417 onto theinjection site, pushing the needle guard 417 into the autoinjector body401, inserting the needle 402 into the patient and unlocking the plunger407, allowing the spring to drive the plunger 407 downwards to expel thedrug from the first chamber 405. Although the above example statescompressing the delivery spring when drawing the drug back into theautoinjector 400 it is also possible for the spring to be compressedduring manufacturing.

In a further alternative embodiment the mixture comprising the firstdrug component and the second drug component can be transferred back andforth between the first chamber 305, 405 of the autoinjector or syringeand the second chamber 309, 409 of the vial 308, 408. Thereby, therespective needle 302, 402 preferably creates water jet during transfer,promoting mixing or reconstitution.

Before the user injects the mixed or reconstituted drug the user mayprime the syringe 300 manually. In another embodiment instead of primingthe syringe 300 manually, the base station can be provided with arespective feature to prime the syringe 300. This can be done, forexample, by using the second drive mechanism which axially moves theplunger 307 a small distance, whilst holding housing 301 still, so thatany air in the syringe is expelled. The same applies to the autoinjector400, wherein the autoinjector may either be powered by air pressure or aconventional mechanical spring.

The main advantage of the above described inventive drug reconstitutionsystem with a base station 350, 450, a syringe 300 or autoinjector 400,a supporting unit 310, 410 and a vial 308, 408 consists therein, that itautomates the reconstitution operation, thereby removing all manualsteps. If a transducer 371, 471 is provided in the base station 350, 450it improves the consistency and repeatability of reconstitution. Thesystem further reduces the number of devices presented to the user andremoves the need to disinfect the drug vial 308, 408. Additionally, itreduces the chance of injecting air into the patient. With regard to theautoinjector version, wherein the base station 450 primes theautoinjector 400 right before use there is the advantage that thisallows the autoinjector 400 to be stored and transported without stress,reducing the complexity of the autoinjector 400 and the risk of misfireand failure.

REFERENCE NUMBERS

-   100, 200, 300, 500 syringe-   101, 201, 301, 351, 501, 510 a housing-   101 a ratchet-   101 b return track-   102, 202, 302, 402, 502 needle-   105, 205, 305, 405, 505 first chamber-   107, 207, 307, 407, 507 plunger-   107 a clip member-   108 distal end section-   109, 209, 309, 409, 509 second chamber-   111, 511 lower piston-   112, 512 upper piston-   112 a clip member-   113 handle-   114 through hole-   115, 315, 415 needle boot-   117 cotter pin-   120 rib-   122 needle-   125 membrane-   210 slug-like element-   210 a distal end-   210 b proximal end-   211, 313, 413 seal-   213 arrow-   214 arrow-   215 needle cover-   220 element-   250, 350, 450 base station-   260 electromagnetic unit-   260 a electromagnetic coil-   260 b steel pole piece-   262 line of magnetic field-   265 opening-   270 control unit-   275 button-   308, 408 vial-   310, 410 supporting unit-   310 a, 310 b, 410 a, 410 b part of supporting unit-   311, 411 first recess-   312, 412 second recess-   365, 465, 511 a recess-   366, 466 platform face-   370, 470 drive unit-   371, 471 transducer-   372, 472 heater element-   374 first linear slide-   375 second linear slide-   400 autoinjector-   401 autoinjector body-   414 air chamber-   417 needle guard-   418 septum-   419 spring-   420 locking mechanism-   473 air pump-   513 projection-   530 compression spring-   535 cap-   536 clip mechanism-   538 O-ring-   540, 541, 542 arrow

The invention claimed is:
 1. A base station that is part of a mixingand/or reconstitution system that comprises the base station, a device,a vial, a needle, and a sleeve-like supporting unit, wherein the devicecontains a first material within a first chamber and comprises a devicehousing and a plunger, wherein the vial contains a second materialwithin a second chamber, wherein at least one of the first material andthe second material is a fluid, wherein a self-supporting assembly isformed by the sleeve-like supporting unit and further comprises thedevice, the vial, and the needle, wherein the sleeve-like supportingunit is adapted to fix the device and the vial at pre-defined relativepositions, wherein the needle is attached to the device and fluidlyconnected with the first chamber of the device, the base stationcomprising: at least one drive unit; a first slide; a driver; a housing;and an unlocking feature, wherein the base station is configured suchthat the self-supporting assembly, is attachable to the base stationsuch that the device, the vial, and the needle are attachable to thebase station in an initial position, in which the device and the vialhave a pre-defined distance between each other, wherein in the initialposition the at least one drive unit is connected to the first slidethat moves the vial and/or the device housing relative to each other inan axial direction of the device into an activated position, wherein inthe activated position: the needle is fluidly connected with the secondchamber, and the at least one drive unit is connected to the driver thatmoves the plunger in the axial direction of the device such that duringa fluid connection of the needle with the second chamber the firstmaterial is expelled from the first chamber of the device into thesecond chamber of the vial, or the second material is expelled from thesecond chamber of the vial into the first chamber of the device, or boththe first material is expelled into the second chamber and the secondmaterial is expelled into the first chamber, wherein an upper side ofthe housing of the base station has a recess that is adapted to receiveand releasably fix the self-supporting assembly when the device and thevial are locked within the sleeve-like supporting unit, and wherein theunlocking feature is configured to unlock parts of the sleeve-likesupporting unit, allowing the device housing and the vial to moverelative to each other when the self-supporting assembly is received andreleasably fixed by the recess of the housing of the base station,wherein the sleeve-like supporting unit is positioned within the recessof the base station.
 2. The base station according to claim 1, furthercomprising: a vibrating unit adapted to vibrate at a frequency between60 Hz and 50 kHz, and adapted to transmit a mechanical vibration to thevial of the self-supporting assembly or to the device, when theself-supporting assembly is in the activated position.
 3. The basestation according to claim 2, wherein the vibrating unit is adapted tovibrate at a frequency between 60 Hz and 200 Hz or between 10 kHz and 50kHz.
 4. The base station according to claim 1, further comprising aheater element adapted to heat the first chamber, the second chamber, orboth when the self-supporting assembly is in the activated position. 5.A mixing and/or reconstitution system comprising: a device containing afirst material within a first chamber, and further comprising a devicehousing and a plunger; a vial containing a second material within asecond chamber, wherein at least one of the first material and thesecond material is a fluid; a needle; a sleeve-like supporting unitwhich is adapted to form a self-supporting assembly comprising thedevice, the vial, and the needle, wherein the sleeve-like supportingunit is adapted to fix the device and the vial at pre-defined relativepositions; and a base station comprising at least one drive unit, afirst slide, a driver, a housing, and an unlocking feature, wherein anupper side of the housing of the base station has a recess that isadapted to receive and releasably fix the self-supporting assembly whenthe device and the vial are locked within the sleeve-like supportingunit, and wherein the unlocking feature is configured to unlock parts ofthe sleeve-like supporting unit, allowing the device housing and thevial to move relative to each other when the self-supporting assembly isreceived and releasably fixed by the recess of the housing of the basestation, wherein the sleeve-like supporting unit is positioned withinthe recess of the base station, wherein the needle is attached to thedevice, and is fluidly connected with the first chamber of the device,wherein the self-supporting assembly is attachable to the base stationin an initial position of the device and the vial, wherein in theinitial position, the device and the vial are attachable to the basestation such that the device and the vial have a pre-defined distancebetween each other, wherein in the initial position the at least onedrive unit is connected to the first slide that moves the vial and/orthe device housing relative to each other in an axial direction of thedevice into an activated position, wherein in the activated position:the needle is fluidly connected with the second chamber, and the atleast one drive unit is connected to the driver that moves the plungerin the axial direction of the device such that during a fluid connectionof the needle with the second chamber the first material is expelledfrom the first chamber of the device into the second chamber of thevial, or the second material is expelled from the second chamber of thevial into the first chamber of the device, or both the first material isexpelled into the second chamber and the second material is expelledinto the first chamber.
 6. The system according to claim 5, wherein theself-supporting assembly further comprises a needle boot that isattached to the device and covers the needle.
 7. The system according toclaim 5, wherein the at least one drive unit is connected to the driversuch that during the fluid connection of the needle with the secondchamber, the first material is expelled from the first chamber of thedevice into the second chamber of the vial to form a mixed and/orreconstituted drug by the first material and the second material, andsubsequently, at least a pre-defined fraction of the mixed and/orreconstituted drug is discharged from the second chamber of the vialinto the first chamber of the device.
 8. The system according to claim5, wherein the device is an autoinjector comprising a needle guard and amechanism coupled to the needle guard which unlocks the plunger, whereinthe autoinjector comprises a fluid chamber which hermetically seals aproximal end of the autoinjector with the plunger, and wherein the basestation comprises a fluid pump, wherein the fluid pump is fluidlyconnected to the fluid chamber in the activated position.
 9. The systemaccording to claim 5, wherein the base station comprises a vibratingunit adapted to vibrate at a frequency between 60 Hz and 50 kHz, andadapted to transmit a mechanical vibration to the vial of theself-supporting assembly or to the device, when the self-supportingassembly is in the activated position.
 10. The system according to claim9, wherein the vibrating unit is adapted to vibrate at a frequencybetween 60 Hz and 200 Hz or between 10 kHz and 50 kHz.
 11. A mixingand/or reconstitution method comprising: attaching a needle to a deviceand fluidly connecting the needle to a first chamber of the device,wherein the device contains a first material within the first chamber,and further comprises a device housing and a plunger; attaching thedevice with the needle, and a vial to a base station in an initialposition in which the device and the vial have a pre-defined distancebetween each other, wherein the vial contains a second material within asecond chamber, wherein at least one of the first material and thesecond material is a fluid; in the initial position, moving the vialand/or the device housing relative to each other in a first axialdirection of the device into an activated position, in which the needleis fluidly connected with the second chamber; and in the activatedposition, mixing and/or reconstituting a drug by moving the plunger inthe first axial direction of the device such that during fluidconnection of the needle with the second chamber the first material isexpelled from the first chamber of the device into the second chamber ofthe vial or the second material is expelled from the second chamber ofthe vial into the first chamber of the device, wherein prior to theinitial position a self-supporting assembly comprising the device, thevial, the needle and a sleeve-like supporting unit is formed, whereinthe needle is attached to the device and is fluidly connected with thefirst chamber of the device, and wherein the sleeve-like supporting unitfixes the device and the vial at pre-defined relative positions, andwherein the base station comprises at least one drive unit, a firstslide, a driver, a housing, and an unlocking feature, wherein an upperside of the housing of the base station has a recess that is adapted toreceive and releasably fix the self-supporting assembly when the deviceand the vial are locked within the sleeve-like supporting unit, andwherein the unlocking feature unlocks parts of the sleeve-likesupporting unit, allowing the device housing and the vial to moverelative to each other when the self-supporting assembly is received andreleasably fixed by the recess of the device housing, wherein thesupporting unit is positioned within the recess of the base station. 12.The method according to claim 11, further comprising: after mixingand/or reconstituting of the drug in the activated position, moving thevial and/or the device housing in a second axial direction of the devicesuch that the needle is fluidly disconnected from the second chamber.13. The method according to claim 11, further comprising: during formingthe self-supporting assembly, attaching a needle boot to the device suchthat the needle boot covers the needle.
 14. The method according toclaim 13, wherein the needle boot is collapsed when the vial and/or thehousing are moved relative to each other in the first axial directionprior to the needle being fluidly connected with the second chamber. 15.The method according to claim 11, wherein the mixing and/orreconstituting the drug is conducted in the second chamber of the vial,and the method further comprises after a pre-determined time of mixingand/or reconstituting of the drug, moving the plunger along a secondaxial direction of the device by the drive unit such that at least apre-defined fraction of the drug is discharged from the vial into thefirst chamber of the device.
 16. The method according to claim 11further comprising fixing the self-supporting assembly at the basestation, wherein the device is an autoinjector comprising a needleguard, a mechanism coupled to the needle guard which unlocks theplunger, and a fluid chamber hermetically sealing a proximal end of theautoinjector with the plunger, and wherein a fluid pump of the basestation is fluidly connected with the fluid chamber during fixing theself-supporting assembly at the base station in the activated position.17. The method according to claim 11, wherein the base station comprisesa vibrating unit adapted to vibrate at a frequency between 60 Hz and 50kHz, and wherein the method further comprises transmitting a mechanicalvibration to the vial of the self-supporting assembly or the deviceafter the first material is expelled from the first chamber and into thesecond chamber of the vial or after the second material is expelled fromthe second chamber of the vial into the first chamber of the device. 18.The method according to claim 17, wherein the vibrating unit is adaptedto vibrate at a frequency between 60 Hz and 200 Hz or between 10 kHz and50 kHz.
 19. The method according claim 11, wherein the base stationcomprises a heater element, and wherein the method further comprisesheating, by the heater element, the first chamber and/or the secondchamber when the self-supporting assembly is in the activated position.20. The method according to claim 19, wherein the second chamber isheated after the first material is expelled from the first chamber intothe second chamber.